We have characterized thermodynamically th polymerization and gelation of deoxygenated sickle cell hemoglobin at four temperatures and have calculated entropies and enthalpies of gelation. From measurements of chemical potentials beyond the gel phase transition over a wide concentration range we can separate for the first time the work of polymerization from that of concentrating and orienting gel fibers. Osmotic stress studies should yield not only information about the efficacy of gelation-inhibiting agents but clues as to their mechanism of action and about intermolecular interaction energies. Theories of polymerization and alignment of deoxyhemoglobin S can not only be tested by osmotic stress results, but such thermodynamic data can be used to guide theoretical development of models for the gelation process.